Human articular cartilage repair: Sources and detection of cytotoxicity and genotoxicity in photo-crosslinkable hydrogel bioscaffolds

Abstract

Three‐dimensional biofabrication using photo‐crosslinkable hydrogel bioscaffolds has the potential to revolutionize the need for transplants and implants in joints, with articular cartilage being an early target tissue. However, to successfully translate these approaches to clinical practice, several barriers must be overcome. In particular, the photo‐crosslinking process may impact on cell viability and DNA integrity, and consequently on chondrogenic differentiation. In this review, we primarily explore the specific sources of cellular cytotoxicity and genotoxicity inherent to the photo‐crosslinking reaction, the methods to analyze cell death, cell metabolism, and DNA damage within the bioscaffolds, and the possible strategies to overcome these detrimental effects.

Molecular Insights Into Lysyl Oxidases in Cartilage Regeneration and Rejuvenation

“…Until now, the etiology and pathophysiology of OA have not been well documented. Various treatments, such as cellular therapies (Fu et al, 2014;Lee and Wang, 2017;Lin et al, 2017;Teo et al, 2019;Xu et al, 2019), administration of certain drugs or chemicals (Zhang et al, 2016(Zhang et al, , 2019Yao et al, 2019), therapeutic surgeries (Chen Y. et al, 2015), and biofabrication approach (Tatman et al, 2015;Onofrillo et al, 2018;Lee et al, 2019), have been intensely studied and tested in various preclinical studies and clinical trials during recent decades (Lee and Wang, 2017;Zhang et al, 2019). However, several hurdles are required to be addressed for therapeutic optimization before clinical translation.…”

The Photoinitiator Lithium Phenyl (2,4,6-Trimethylbenzoyl) Phosphinate with Exposure to 405 nm Light Is Cytotoxic to Mammalian Cells but Not Mutagenic in Bacterial Reverse Mutation Assays

“…For example, underexposure would result in imprecise control of the mechanical properties and an increase in the concentration of unreacted monomer, while overexposure would expose cells to additional phototoxic effects while not significantly affecting the mechanical properties. Multiple studies report photopolymer tissue engineering constructs with low cytotoxicity, and/or the ability of cells to proliferate within the construct after printing [ 28 , 36 , 37 ]. The success of this technique is contrary to the assumption that free-radical generating photoinitiators produce toxic effects, including genotoxicity, from reactive oxygen species [ 14 , 38 ].…”

Methylcellulose – a versatile printing material that enables biofabrication of tissue equivalents with high shape fidelity

“…printing into a gelatin microparticle-based support bath). 10 However, these approaches are limited in the choice of materials and application, due to the high technical efforts which need to be performed, the unclear/potentially harmful effect of photoinitiators on cells 11 or the simple circumstance that stiff (supporting) materials will not be applicable for soft tissues.…”